Various asymmetric synthesis reactions are known to be effective for the organic synthesis of natural substances and their analogs. Although some asymmetric catalysts used in such asymmetric synthesis reactions have high activity and promote the intended reaction with high selectivity, many are liable to decomposition and inactivation due to external causes such as oxygen, water, light and heat, and are thus unstable. Hence, most asymmetric catalysts must be prepared from stable precursors immediately before use, and asymmetric catalysts that are stable, storable for a long period of time, recoverable and reusable after reaction, are rare.
The inventors of the present application have developed and reported a chiral zirconium catalyst useful for asymmetric Mannich reaction, and the like (for example, Japanese Patent Application No. 9-197589; Ishitani, H., Ueno, M., and Kobayashi, S., J. Am. Chem., vol. 122, p. 8180 (2000)). However, such chiral zirconium catalyst was also unstable in air and in the presence of water, and use after long-term storage, as well as recovery and reuse after reaction was substantially impossible. Accordingly, in most reaction systems, the catalysts are prepared and used in situ for each reaction.
If a chiral zirconium catalyst could be prepared in advance and stored for a long period of time, the number of process steps for synthesis can be reduced, and for example, in the case of asymmetric Mannich reaction, the operation can be further simplified. Further, if the catalyst could be recovered and reused, not only will it lead to a reduction of cost for the synthesis reaction, but would also lead to a reduction in the amount of metal-containing waste solution, and is thus useful from an environmental viewpoint.
Therefore, the object of the present invention is to solve the aforementioned problems by providing a highly practical chiral zirconium catalyst, which maintains high catalytic activity even after long-term storage, is stable, and can be recovered and reused after reaction.